Graft-versus-host disease is the primary cause of failure of allogeneic transplant. The problem of GVHD is made even more pressing by the increasing transplantation of high risk groups, such as relapsed/refractory disease patients, older patients, patients with mismatch donors, and unrelated donors. We plan to extend our clinical GVHD studies begun during the last grant period. Acute GVHD--We will complete our current Phase I trial of cyclosporine + methotrexate + thalidomide. This trial is a pharmacologic trial designed to ensure we achieve adequate absorption of thalidomide. If this trial is successful, we plan to compare cyclosporine + methotrexate to the same drugs with thalidomide. This trial should show if thalidomide adds to standard GVHD prophylaxis. In another section of the GVHD grant, we will complete the evaluation of rapamycin, a new immunosuppressive, in our animal model. If this is successful, we will plan to first examine rapamycin in treatment of refractory acute GVHD. If rapamycin shows evidence of activity, we will then evaluate the drug in combination therapy in high risk acute GVHD. In chronic GVHD we will compare thalidomide to prednisone in standard risk patients. For patients with high risk or refractory GVHD, we will look at triple therapy using cyclosporine thalidomide and PUVA. We are evaluating this regimen as a steroid sparing regimen. Patients included on all of these protocols will also be evaluated in the laboratory. We will determine if patients receiving thalidomide have altered levels of adhesion molecules on either lymphocytes or skin. Data from the patients will be correlated with extensive animals and laboratory studies on the effects of thalidomide on adhesions molecules. Likewise samples from patients will be studied in other sections of the GVHD grant the entire program project.